title: Differential gene expression profiles of POMC-related enzymes, transcription factors and receptors between non-pituitary and pituitary ACTH-secreting tumors.
abstract: The differential gene expression of proopiomelanocortin (POMC)-related processing enzymes, transcription factors, and receptors responsible for ACTH secretion between non-pituitary and pituitary ACTH-secreting tumors remains obscure. This study was attempted to determine the gene expression profiles of transcription factors (Tpit, NeuroD1 and IKZF1), proprotein convertase (PC) 1/3 and PC2, and several key receptors linked to ACTH secretion, including corticotrophin releasing hormone receptor (CRHR1), vasopressin receptor 1b (V1bR), somatostatin receptor (SSTR) subtype-2, -5 and dopamine receptor type 2 (D2R) in non-pituitary and pituitary ACTH-secreting tumors. Surgical tissue specimens from carcinoid tumors causing ectopic ACTH syndrome (EAS: n=4) and pituitary tumors causing Cushing's disease (CD: n=13), were subjected to real-time RT-PCR for measurements of each mRNA levels. POMC and CRHR1 mRNA levels in CD were far greater than those in EAS, whereas IKZF1, PC2, SSTR-2 and -5 mRNA levels in EAS were significantly greater than those in CD. NeuroD1, Tpit, PC1/3, V1bR and D2R mRNA levels were comparable between EAS and CD. In conclusion, differential gene expression profiles revealed more abundant mRNA expression in EAS than in CD of 1) IKZF1 with its potential implication of cell differentiation and hormone secretion, 2) PC2 with its possible enhanced processing activity of mature ACTH, and 3) SSTR-2 and -5 with their potential therapeutic application of more selective agonists in EAS patients.
authors.affiliation: Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tani
authors.forename: Toru
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Hajime
authors.initials: H
authors.lastname: Izumiyama
authors.forename: Takanobu
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Shozo
authors.initials: S
authors.lastname: Yamada
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D000182:ACTH Syndrome, Ectopic / Q000150:complications / Q000378:metabolism*; D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics* / Q000378:metabolism; D047748:Pituitary ACTH Hypersecretion / Q000209:etiology / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D045706:Proprotein Convertase 2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C497239:IKZF1 protein, human; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D017481:Receptors, Somatostatin; D017483:Receptors, Vasopressin; D014157:Transcription Factors; D051740:Ikaros Transcription Factor; D011333:Pro-Opiomelanocortin; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2; D045706:Proprotein Convertase 2